title: Indolo[2,1-a]isoquinolines. Syntheses, steroid hormone receptor binding affinities, and cytostatic activity.
abstract: A number of acetoxy-substituted 5,6-dihydroindolo[2,1-a]isoquinolines were synthesized and tested for binding affinity for steroid hormone receptors. All of the derivatives bind to the estrogen receptor with RBA values ranging from 1.5 to 17 (17 beta-estradiol = 100). Some of them show binding affinities for the androgen receptor as well. In the mouse uterine weight test, the tetracycles proved to be weak estrogens with partial antagonistic activity. All of the compounds were tested in vitro for cytostatic activity with hormone-independent MDA-MB 231 and hormone-dependent MCF-7 breast cancer cells. A cytostatic effect was found in both cell lines. The comparison of results exhibited a stronger inhibitory effect on MCF-7 cells only for compounds with high binding affinity for the estrogen receptor. For those derivatives, it can be assumed that the growth inhibition is partly mediated by the estrogen receptor.
authors.affiliation: Institut für Pharmazie, Universität Regensburg, Federal Republic of Germany.
authors.forename: R
authors.initials: R
authors.lastname: Ambros
authors.forename: M R
authors.initials: MR
authors.lastname: Schneider
authors.forename: S
authors.initials: S
authors.lastname: von Angerer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000188:drug therapy; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D007546:Isoquinolines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D012669:Seminal Vesicles / Q000033:anatomy & histology; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D007546:Isoquinolines; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol